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Pleiotropic effects of HMG-CoA reductase inhibitors.
Curr Opin Investig Drugs. 2002 Sep; 3(9):1312-7.CO

Abstract

HMG-CoA reductase, in addition to being the rate-limiting enzyme in the cholesterol biosynthetic pathway, is involved in the regulation of receptors for low-density lipoprotein (LDL)-cholesterol. Clinical studies in men and women demonstrate that inhibitors of HMG-CoA reductase (statins), by reducing plasma cholesterol, may limit the development of atherosclerosis and reduce the risk of mortality and ischemic events. Preclinical evidence suggests that under controlled conditions of plasma cholesterol lowering, statins may have ancillary properties or pleiotropic effects, which may directly limit atherosclerosis progression. In this review, pleiotropic effects have been defined as 'ancillary properties of statins, which result in hepatic and/or vascular changes that may or may not be a consequence of inhibition of HMG-CoA reductase.' Beyond the LDL lowering activity of statins, improvements have been noted in endothelial dysfunction through direct stimulation of expression of such vasodilators as nitric oxide and/or reduction in vasoconstrictors. Factors associated with atherogenesis, such as monocyte adhesion to endothelial cells, macrophage production of proinflammatory molecules and matrix metalloproteases, smooth muscle cell proliferation and migration and macrophage-induced oxidation of LDL particles have also been reduced by various statins. It is unclear whether the observed pleiotropic effects are independent of LDL-cholesterol lowering or inhibition of HMG-CoA reductase, and whether they are clinically relevant; however, one can conclude that the pleiotropic effects appear to be a class effect of statins and can be attenuated by addition of the post-reductase product, mevalonate.

Authors+Show Affiliations

BioImaging Center, Pfizer Global Research and Development, Pfizer Inc, 2800 Plymouth Road, Ann Arbor, MI 48105, USA. Thomas.Bocan@pfizer.com

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

12498006

Citation

Bocan, Thomas M A.. "Pleiotropic Effects of HMG-CoA Reductase Inhibitors." Current Opinion in Investigational Drugs (London, England : 2000), vol. 3, no. 9, 2002, pp. 1312-7.
Bocan TM. Pleiotropic effects of HMG-CoA reductase inhibitors. Curr Opin Investig Drugs. 2002;3(9):1312-7.
Bocan, T. M. (2002). Pleiotropic effects of HMG-CoA reductase inhibitors. Current Opinion in Investigational Drugs (London, England : 2000), 3(9), 1312-7.
Bocan TM. Pleiotropic Effects of HMG-CoA Reductase Inhibitors. Curr Opin Investig Drugs. 2002;3(9):1312-7. PubMed PMID: 12498006.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pleiotropic effects of HMG-CoA reductase inhibitors. A1 - Bocan,Thomas M A, PY - 2002/12/25/pubmed PY - 2003/5/28/medline PY - 2002/12/25/entrez SP - 1312 EP - 7 JF - Current opinion in investigational drugs (London, England : 2000) JO - Curr Opin Investig Drugs VL - 3 IS - 9 N2 - HMG-CoA reductase, in addition to being the rate-limiting enzyme in the cholesterol biosynthetic pathway, is involved in the regulation of receptors for low-density lipoprotein (LDL)-cholesterol. Clinical studies in men and women demonstrate that inhibitors of HMG-CoA reductase (statins), by reducing plasma cholesterol, may limit the development of atherosclerosis and reduce the risk of mortality and ischemic events. Preclinical evidence suggests that under controlled conditions of plasma cholesterol lowering, statins may have ancillary properties or pleiotropic effects, which may directly limit atherosclerosis progression. In this review, pleiotropic effects have been defined as 'ancillary properties of statins, which result in hepatic and/or vascular changes that may or may not be a consequence of inhibition of HMG-CoA reductase.' Beyond the LDL lowering activity of statins, improvements have been noted in endothelial dysfunction through direct stimulation of expression of such vasodilators as nitric oxide and/or reduction in vasoconstrictors. Factors associated with atherogenesis, such as monocyte adhesion to endothelial cells, macrophage production of proinflammatory molecules and matrix metalloproteases, smooth muscle cell proliferation and migration and macrophage-induced oxidation of LDL particles have also been reduced by various statins. It is unclear whether the observed pleiotropic effects are independent of LDL-cholesterol lowering or inhibition of HMG-CoA reductase, and whether they are clinically relevant; however, one can conclude that the pleiotropic effects appear to be a class effect of statins and can be attenuated by addition of the post-reductase product, mevalonate. SN - 1472-4472 UR - https://www.unboundmedicine.com/medline/citation/12498006/Pleiotropic_effects_of_HMG_CoA_reductase_inhibitors_ L2 - https://medlineplus.gov/cholesterolmedicines.html DB - PRIME DP - Unbound Medicine ER -